Genetic Variant CNTNAP5:p.Ser137Arg (chr2-124417472-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001367498.1(CNTNAP5):c.411C>A(p.Ser137Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S137S) has been classified as Benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

CNTNAP5
NM_001367498.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.63

Publications

0 publications found

Variant links:

Genes affected

CNTNAP5 (HGNC:18748): (contactin associated protein family member 5) This gene product belongs to the neurexin family, members of which function in the vertebrate nervous system as cell adhesion molecules and receptors. This protein, like other neurexin proteins, contains epidermal growth factor repeats and laminin G domains. In addition, it includes an F5/8 type C domain, discoidin/neuropilin- and fibrinogen-like domains, and thrombospondin N-terminal-like domains. [provided by RefSeq, Jul 2008]

CNTNAP5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.826

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP5	NM_001367498.1 link	c.411C>A	p.Ser137Arg	missense_variant	Exon 4 of 24	ENST00000682447.1	NP_001354427.1
CNTNAP5	NM_130773.4 link	c.411C>A	p.Ser137Arg	missense_variant	Exon 4 of 24		NP_570129.1	Q8WYK1
CNTNAP5	XM_017003316.2 link	c.411C>A	p.Ser137Arg	missense_variant	Exon 4 of 23		XP_016858805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP5	ENST00000682447.1 link	c.411C>A	p.Ser137Arg	missense_variant	Exon 4 of 24		NM_001367498.1	ENSP00000508115.1		A0A804HKY0
CNTNAP5	ENST00000431078.1 link	c.411C>A	p.Ser137Arg	missense_variant	Exon 4 of 24	1		ENSP00000399013.1		Q8WYK1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461590

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727060

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86222

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111806

Other (OTH)

AF:

0.00

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

2.3

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.67

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.049

LIST_S2

Uncertain

0.91

M_CAP

Uncertain

0.19

MetaRNN

Pathogenic

0.83

MetaSVM

Uncertain

0.73

MutationAssessor

Uncertain

2.4

PhyloP100

-2.6

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-4.0

REVEL

Uncertain

0.58

Sift

Benign

0.034

Sift4G

Uncertain

0.0060

Polyphen

0.99

Vest4

0.80

MutPred

0.63

Gain of MoRF binding (P = 0.0135);

MVP

0.43

MPC

0.48

ClinPred

0.98

GERP RS

-7.2

Varity_R

0.56

gMVP

0.59

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over